Chromosome-wide mechanisms to decouple gene expression from gene dose during sex-chromosome evolution
- Rhodes College, United States
- Howard Hughes Medical Institute, University of California, Berkeley, United States
- Stanford University, United States
- Howard Hughes Medical Institute, University of Utah, United States
Abstract
Changes in chromosome number impair fitness by disrupting the balance of gene expression. Here we analyze mechanisms to compensate for changes in gene dose that accompanied the evolution of sex chromosomes from autosomes. Using single-copy transgenes integrated throughout the Caenorhabditis elegans genome, we show that expression of all X-linked transgenes is balanced between XX hermaphrodites and XO males. However, proximity of a dosage compensation complex (DCC) binding site (rex site) is neither necessary to repress X-linked transgenes nor sufficient to repress transgenes on autosomes. Thus, X is broadly permissive for dosage compensation, and the DCC acts via a chromosome-wide mechanism to balance transcription between sexes. In contrast, no analogous X-chromosome-wide mechanism balances transcription between X and autosomes: expression of compensated hermaphrodite X-linked transgenes is half that of autosomal transgenes. Furthermore, our results argue against an X-chromosome dosage compensation model contingent upon rex-directed positioning of X relative to the nuclear periphery.
Data availability
-
SRR023579.sraPublicly available at the Sequence Read Archive + (accession no: GSE20136).
-
Transcriptome Analysis of roundwormPublicly available at the NCBI Short Read Archive (accession no: GSE20136).
-
Condensin Controls Recruitment of RNA Polymerase II to Achieve X-Chromosome Dosage CompensationPublicly availale at the NCBI Gene Expression Omnibus (accession no: GSE43087).
-
SRR031122.sraPublicly available at the Sequence Read Archive + (accession no: GSE20136).
-
SRR031123.sraPublicly available at the Sequence Read Archive + (accession no: GSE20136).
-
Condensin-Driven Remodeling of X-Chromosome Topology during Dosage CompensationPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE59716).
Article and author information
Author details
Funding
National Institutes of Health (1R01 GM030702)
- Barbara J Meyer
Howard Hughes Medical Institute
- Barbara J Meyer
National Institutes of Health (1F32 GM100647)
- Bayly S Wheeler
Howard Hughes Medical Institute
- Christian Frøkjær-Jensen
National Institutes of Health (1R01 GM095817)
- Erik Jorgensen
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Edith Heard, Institut Curie, France
Version history
- Received: April 29, 2016
- Accepted: August 29, 2016
- Accepted Manuscript published: August 30, 2016 (version 1)
- Accepted Manuscript updated: September 1, 2016 (version 2)
- Version of Record published: October 3, 2016 (version 3)
Copyright
© 2016, Wheeler et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 2,467
- views
-
- 405
- downloads
-
- 27
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Chromosome-wide mechanisms to decouple gene expression from gene dose during sex-chromosome evolution
eLife 5:e17365.
https://doi.org/10.7554/eLife.17365
Further reading
-
- Biochemistry and Chemical Biology
- Chromosomes and Gene Expression
Recent findings indicate that the translation elongation rate influences mRNA stability. One of the factors that has been implicated in this link between mRNA decay and translation speed is the yeast DEAD-box helicase Dhh1p. Here, we demonstrated that the human ortholog of Dhh1p, DDX6, triggers the deadenylation-dependent decay of inefficiently translated mRNAs in human cells. DDX6 interacts with the ribosome through the Phe-Asp-Phe (FDF) motif in its RecA2 domain. Furthermore, RecA2-mediated interactions and ATPase activity are both required for DDX6 to destabilize inefficiently translated mRNAs. Using ribosome profiling and RNA sequencing, we identified two classes of endogenous mRNAs that are regulated in a DDX6-dependent manner. The identified targets are either translationally regulated or regulated at the steady-state-level and either exhibit signatures of poor overall translation or of locally reduced ribosome translocation rates. Transferring the identified sequence stretches into a reporter mRNA caused translation- and DDX6-dependent degradation of the reporter mRNA. In summary, these results identify DDX6 as a crucial regulator of mRNA translation and decay triggered by slow ribosome movement and provide insights into the mechanism by which DDX6 destabilizes inefficiently translated mRNAs.
-
- Chromosomes and Gene Expression
Tardigrades are microscopic animals renowned for their ability to withstand extreme conditions, including high doses of ionizing radiation (IR). To better understand their radio-resistance, we first characterized induction and repair of DNA double- and single-strand breaks after exposure to IR in the model species Hypsibius exemplaris. Importantly, we found that the rate of single-strand breaks induced was roughly equivalent to that in human cells, suggesting that DNA repair plays a predominant role in tardigrades’ radio-resistance. To identify novel tardigrade-specific genes involved, we next conducted a comparative transcriptomics analysis across three different species. In all three species, many DNA repair genes were among the most strongly overexpressed genes alongside a novel tardigrade-specific gene, which we named Tardigrade DNA damage Response 1 (TDR1). We found that TDR1 protein interacts with DNA and forms aggregates at high concentration suggesting it may condensate DNA and preserve chromosome organization until DNA repair is accomplished. Remarkably, when expressed in human cells, TDR1 improved resistance to Bleomycin, a radiomimetic drug. Based on these findings, we propose that TDR1 is a novel tardigrade-specific gene conferring resistance to IR. Our study sheds light on mechanisms of DNA repair helping cope with high levels of DNA damage inflicted by IR.
